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Analysis on molecular mechanisms of neuralization and early patterning in the formation of the presumptive midbrain-hindbrain boundary region

Research Project

Project/Area Number 16370076
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionThe University of Tokyo

Principal Investigator

TAIRA Masanori  The Univ. of Tokyo, Deprtment of Biological Sciences, Associate Professor, 大学院理学系研究科, 助教授 (60150083)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2005: ¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 2004: ¥8,400,000 (Direct Cost: ¥8,400,000)
Keywordsvertebrates / Xenopus / early development / neuralization / pattern formation / midbrain-hindbrain boundary / transcription factors / XHR1 / ツメガエル
Research Abstract

To explore the molecular mechanism of neuralization and early pattern formation in vertebrate embryos, we investigated the following two subjects.
1) Functional analysis of XHR1 : ESR1 is a bHLH transcriptional repressor gene, and was identified as a candidate for XHR1 target genes. We performed (1) gene activation analysis using a XRH1-VP16-GR construct and a protein synthesis inhibitor, (2) gain-of-function analysis of XHR1 and ESR1, and (3) loss-of-function analysis using antisense-morpholino oligos for XHR1. We showed that ESR is a direct target of XHR1 ; that XHR1 is necessary and sufficient for suppression of ESR1 expression; and that overexpression of ESR1 represses the MHB gene Pax2. Furthermore, in contrast to ESR1, XHR1 was not activated by Notch signaling, and XHR1 directly repressed neuronal genes, neurogenin and delta. These data suggest that XHR1 functions as a prepattern gene for MHB formation as well as for proneural cluster formation by repressing neuronal differentiati … More on
2) Analysis of XHR1 gene regulation : We cloned and analyzed a Xenopus tropicalis HR1 (XtHR1) promoter, which faithfully recapitulated the endogenous XHR1 expression. Surprisingly, transgenic and animal cap assays revealed distinct enhancers, named the early and late enhancer modules (the EEM and LEM), that govern XHR1 expression in pre-MHB and MHB regions, respectively. Furthermore, the EEM was found to integrate Noggin, Wnt, and FGF signals. Gain-of-function and dominant-negative approaches in vivo showed that neural inducers activate XHR1 ; Wnt signaling confines XHR1 expression; and moderate and strong FGF signaling enhances and suppresses XHR1 expression, respectively. These data suggest that the XHR1 expression of the pre-MHB region is induced through the EEM by signaling molecules from the Spemann organizer.
Thus, we have shown the molecular mechanism of XHR1 induction in the pre-MHB region and a molecular cascade mediated by XHR1 from the pre-MHB to the MHB region, an organizing center of brain formation. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (11 results)

All 2005 2004

All Journal Article (8 results) Book (3 results)

  • [Journal Article] Identification of target genes for the Xenopus Hes-related protein XHR1, a prepattern factor specifying the midbrain-hindbrain boundary2005

    • Author(s)
      Takada, H., Hattori, D., Kitayama, A., Ueno, N., Taira, M.
    • Journal Title

      Dev. Biol. 283

      Pages: 253-267

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of target genes for the Xenopus Hes-related protein XHR1, a prepattern factor specifying the midbrain-hindbrain boundary2005

    • Author(s)
      Takada, H., Hattori, D., Kitayama, A., Ueno, N., Taira, M.
    • Journal Title

      Dev.Biol. 283

      Pages: 253-267

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification target genes for the Xenopus Hes-related protein XHR1, a prepattern factor specifying the midbrain-hindbrain boundary2005

    • Author(s)
      Hitomi Takada
    • Journal Title

      Dev.Biol. 283

      Pages: 253-267

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Role of Crescent in convergent extension movements by modulating Wnt signaling in early Xenopus embryogenesis2005

    • Author(s)
      Mikihito Shibata
    • Journal Title

      Mech.Dev. 122

      Pages: 1322-1339

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Systematic screening for genes specifically expressed in the anterior neuroectoderm during early Xenopus development2005

    • Author(s)
      Noriyuki Takahashi
    • Journal Title

      Int.J.Dev.Biol. 49

      Pages: 939-951

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression patterns of Xenopus FGF receptor-like 1/nou-darake in early Xenopus development resemble those of planarian nou-darake and Xenopus FGF82004

    • Author(s)
      S.Hayashi, M.Itoh, S.Taira, K.Agata, M.Taira
    • Journal Title

      Dev.Dyn. 230

      Pages: 700-707

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cellular FLIP inhibits beta-catenin ubiquitylation and enhances Wnt signaling2004

    • Author(s)
      Naito, M., Katayama, R., Ishioka, T., Suga, A., Takubo, K., Nanjo, M.et al.
    • Journal Title

      Mol.Cell.Biol. 24

      Pages: 8418-8427

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Excision of the Tol2 transposable element of the medaka fish Oryzias latipes in Xenopus laevis and Xenopus tropicalis2004

    • Author(s)
      Kawakami, K., Imanaka, K., Itoh, M., Taira, M.
    • Journal Title

      Gene 338

      Pages: 93-98

    • Related Report
      2004 Annual Research Report
  • [Book] 細胞生物学事典(項目 : エンハンサー、基本転写因子、転写、転写調節因子、プロモーター)2005

    • Author(s)
      平良眞規
    • Total Pages
      4
    • Publisher
      朝倉書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 細胞生物学事典2005

    • Author(s)
      平良眞規
    • Total Pages
      16
    • Publisher
      朝倉書店
    • Related Report
      2005 Annual Research Report
  • [Book] 改訂RNAi実験プロトコール(分担執筆:アフリカツメガエル)2004

    • Author(s)
      平良眞規, 伊藤万里
    • Total Pages
      12
    • Publisher
      羊土社
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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